Agonistic Effect of Tamoxifen Is Dependent on Cell Type, ERE-Promoter Context, and Estrogen Receptor Subtype: Functional Difference between Estrogen Receptors α and β

For several decades, it has been known that oestrogens are essential for human health. The discovery that there are two oestrogen receptors (ERs), ERalpha and ERbeta, has facilitated our understanding of how the hormone exerts its physiological effects. The ERs belong to the family of ligand-activated nuclear receptors, which act by modulating the expression of target genes. Studies of ER-knockout (ERKO) mice have been instrumental in defining the relevance of a given receptor subtype in a certain tissue. Phenotypes displayed by ERKO mice suggest diseases in which dysfunctional ERs might be involved in aetiology and pathology. Association between single-nucleotide polymorphisms (SNPs) in ER genes and disease have been demonstrated in several cases. Selective ER modulators (SERMs), which are selective with regard to their effects in a certain cell type, already exist. Since oestrogen has effects in many tissues, the goal with a SERM is to provide beneficial effects in one target tissue while avoiding side effects in others. Refined SERMs will, in the future, provide improved therapeutic strategies for existing and novel indications.

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Impact of estradiol, estrogen receptor subtype specific agonists and genistein on food intake, body weight, and glucose metabolism in leptin resistant ovariectomized Zucker diabetic fatty rats

Experimental and Clinical Endocrinology & Diabetes ◽

10.1055/s-0033-1336633 ◽

2013 ◽

Vol 121 (03) ◽

Author(s):

C Weigt ◽

T Hertrampf ◽

U Flenker ◽

F Hülsemann ◽

KH Fritzemeier ◽

...

Keyword(s):

Estrogen Receptor ◽

Body Weight ◽

Food Intake ◽

Glucose Metabolism ◽

Receptor Subtype ◽

Zucker Diabetic Fatty Rats

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Estrogen receptor subtype-specific repression of calpain-activation in neuronal cells

Pharmacopsychiatry ◽

10.1055/s-2005-918686 ◽

2005 ◽

Vol 38 (05) ◽

Author(s):

M Gamerdinger ◽

D Manthey ◽

C Behl

Keyword(s):

Estrogen Receptor ◽

Neuronal Cells ◽

Receptor Subtype ◽

Calpain Activation

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G Protein-Coupled Estrogen Receptor 1 (GPER) as a Novel Target for Schizophrenia Drug Treatment

Schizophrenia Bulletin Open ◽

10.1093/schizbullopen/sgaa062 ◽

2020 ◽

Vol 1 (1) ◽

Author(s):

Danielle S Macêdo ◽

Lia Lira Olivier Sanders ◽

Raimunda das Candeias ◽

Cyntia de Freitas Montenegro ◽

David Freitas de Lucena ◽

...

Keyword(s):

Estrogen Receptor ◽

Estrogen Receptors ◽

G Protein ◽

Brain Inflammation ◽

Antipsychotic Treatment ◽

New Class ◽

Estrogen Receptor Modulators ◽

Novel Target ◽

G Protein Coupled ◽

Estrogen Receptor 1

Abstract The observation that a person’s sex influences the onset age of schizophrenia, the course of the disease, and antipsychotic treatment response suggests a possible role for estrogen receptors in the pathophysiology of schizophrenia. Indeed, treatment with adjunctive estrogen or selective estrogen receptor modulators (SERMs) are known to reduce schizophrenia symptoms. While estrogen receptors (ER)α and ERβ have been studied, a third and more recently discovered estrogen receptor, the G protein-coupled estrogen receptor 1 (GPER), has been largely neglected. GPER is a membrane receptor that regulates non-genomic estrogen functions, such as the modulation of emotion and inflammatory response. This review discusses the possible role of GPER in brain impairments seen in schizophrenia and in its potential as a therapeutic target. We conducted a comprehensive literature search in the PubMed/MEDLINE database, using the following search terms: “Schizophrenia,” “Psychosis,” “GPER1 protein,” “Estrogen receptors,” “SERMS,” “GPER1 agonism, “Behavioral symptoms,” “Brain Inflammation.” Studies involving GPER in schizophrenia, whether preclinical or human studies, have been scarce, but the results are encouraging. Agonism of the GPER receptor could prove to be an essential mechanism of action for a new class of “anti-schizophrenia” drugs.

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